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Review
. 2025 Apr 25;14(9):640.
doi: 10.3390/cells14090640.

Epigenetic Control of Alveolar Macrophages: Impact on Lung Health and Disease

Nirmal Parajuli  1   2 , Kalpana Subedi  1   2 , Xzaviar Kaymar Solone  1   2 , Aimin Jiang  1   2   3 , Li Zhou  1   2   3   4 , Qing-Sheng Mi  1   2   3   4
Affiliations
Review

Epigenetic Control of Alveolar Macrophages: Impact on Lung Health and Disease

Nirmal Parajuli et al. Cells. .

Abstract

Alveolar macrophages (AMs) are immune cells located in the alveoli-the tiny air sacs in the lungs where gas exchange occurs. Their functions are regulated by various epigenetic mechanisms, which are essential for both healthy lung function and disease development. In the lung's microenvironment, AMs play critical roles in immune surveillance, pathogen clearance, and tissue repair. This review examines how epigenetic regulation influences AM functions and their involvement in lung diseases. Key mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression in response to environmental signals. In healthy lungs, these modifications enable AMs to quickly respond to inhaled threats. However, when these processes malfunction, they could contribute to diseases such as pulmonary fibrosis, COPD, and pulmonary hypertension. By exploring how epigenetic changes affect AM polarization, plasticity, and immune responses, we can gain deeper insights into their role in lung diseases and open new avenues for treating and preventing respiratory conditions. Ultimately, understanding the epigenetic mechanisms within AMs enhances our knowledge of lung immunology and offers potential for innovative interventions to restore lung health and prevent respiratory diseases.

Keywords: DNA methylation; alveolar macrophage; epigenetics; histone modification.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Anatomic localization of various macrophages within the alveoli of normal lung.
Figure 2
Figure 2
Embryonic development of lung alveolar macrophages—insights into origin and differentiation.
Figure 3
Figure 3
Illustrative role of epigenetic mechanisms within lung macrophages for manifesting lung disease.
See this image and copyright information in PMC

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